Novak1998-Model scenarios for evolution of the eukaryotic cell cycle.

Model Identifier
MODEL2005040001
Short description
Progress through the division cycle of present day eukaryotic cells is controlled by a complex network consisting of (i) cyclin-dependent kinases (CDKs) and their associated cyclins, (ii) kinases and phosphatases that regulate CDK activity, and (iii) stoichiometric inhibitors that sequester cyclin-CDK dimers. Presumably regulation of cell division in the earliest ancestors of eukaryotes was a considerably simpler affair. Nasmyth (1995) recently proposed a mechanism for control of a putative, primordial, eukaryotic cell cycle, based on antagonistic interactions between a cyclin-CDK and the anaphase promoting complex (APC) that labels the cyclin subunit for proteolysis. We recast this idea in mathematical form and show that the model exhibits hysteretic behaviour between alternative steady states: a Gl-like state (APC on, CDK activity low, DNA unreplicated and replication complexes assembled) and an S/M-like state (APC off, CDK activity high, DNA replicated and replication complexes disassembled). In our model, the transition from G1 to S/M ('Start') is driven by cell growth, and the reverse transition ('Finish') is driven by completion of DNA synthesis and proper alignment of chromosomes on the metaphase plate. This simple and effective mechanism for coupling growth and division and for accurately copying and partitioning a genome consisting of numerous chromosomes, each with multiple origins of replication, could represent the core of the eukaryotic cell cycle. Furthermore, we show how other controls could be added to this core and speculate on the reasons why stoichiometric inhibitors and CDK inhibitory phosphorylation might have been appended to the primitive alternation between cyclin accumulation and degradation.
Format
SBML
(L2V4)
Related Publication
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Model scenarios for evolution of the eukaryotic cell cycle.
- Novak B, Csikasz-Nagy A, Gyorffy B, Nasmyth K, Tyson JJ
- Philosophical transactions of the Royal Society of London. Series B, Biological sciences , 12/ 1998 , Volume 353 , Issue 1378 , pages: 2063-2076 , PubMed ID: 10098216
- Department of Agricultural Chemical Technology, Technical University of Budapest, Hungary. bnovak@chem.bme.hu
- Progress through the division cycle of present day eukaryotic cells is controlled by a complex network consisting of (i) cyclin-dependent kinases (CDKs) and their associated cyclins, (ii) kinases and phosphatases that regulate CDK activity, and (iii) stoichiometric inhibitors that sequester cyclin-CDK dimers. Presumably regulation of cell division in the earliest ancestors of eukaryotes was a considerably simpler affair. Nasmyth (1995) recently proposed a mechanism for control of a putative, primordial, eukaryotic cell cycle, based on antagonistic interactions between a cyclin-CDK and the anaphase promoting complex (APC) that labels the cyclin subunit for proteolysis. We recast this idea in mathematical form and show that the model exhibits hysteretic behaviour between alternative steady states: a Gl-like state (APC on, CDK activity low, DNA unreplicated and replication complexes assembled) and an S/M-like state (APC off, CDK activity high, DNA replicated and replication complexes disassembled). In our model, the transition from G1 to S/M ('Start') is driven by cell growth, and the reverse transition ('Finish') is driven by completion of DNA synthesis and proper alignment of chromosomes on the metaphase plate. This simple and effective mechanism for coupling growth and division and for accurately copying and partitioning a genome consisting of numerous chromosomes, each with multiple origins of replication, could represent the core of the eukaryotic cell cycle. Furthermore, we show how other controls could be added to this core and speculate on the reasons why stoichiometric inhibitors and CDK inhibitory phosphorylation might have been appended to the primitive alternation between cyclin accumulation and degradation.
Contributors
Submitter of the first revision: Ahmad Zyoud
Submitter of this revision: Ahmad Zyoud
Modellers: Ahmad Zyoud
Submitter of this revision: Ahmad Zyoud
Modellers: Ahmad Zyoud
Metadata information
isDescribedBy (1 statement)
hasProperty (3 statements)
hasTaxon (1 statement)
hasProperty (3 statements)
Mathematical Modelling Ontology
Ordinary differential equation model
Gene Ontology cell cycle
NCIt Cyclin-Dependent Kinase
Gene Ontology cell cycle
NCIt Cyclin-Dependent Kinase
hasTaxon (1 statement)
Curation status
Non-curated
Modelling approach(es)
Tags
Connected external resources
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Model files |
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Novak1998.xml | SBML L2V4 Novak1998-Model scenarios for evolution of the eukaryotic cell cycle_Original | 69.34 KB | Preview | Download |
Additional files |
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Novak1998.cps | COPASI version 4.27 (Build 217) Novak1998-Model scenarios for evolution of the eukaryotic cell cycle_Original | 131.56 KB | Preview | Download |